Quantitative Estimate of Synaptic Inputs to Striatal Neurons during Up and Down States In Vitro

Up states are prolonged membrane potential depolarizations critical for synaptic integration and action potential generation in cortical and striatal neurons. They commonly result from numerous concurrent synaptic inputs, whereas neurons reside in a down state when synaptic inputs are few. By quantifying the composition, frequency, and amplitude of synaptic inputs for both states, we provide important constraints for state transitions in striatal network dynamics. Up and down states occur naturally in cortex-striatum-substantia nigra cocultures, which were used as an in vitro model in the present study. Spontaneous synaptic inputs during down states were extracted automatically in spiny projection neurons and fast spiking interneurons of the striatum using a newly developed computer algorithm. Consistent with a heterogeneous population of synaptic inputs, PSPs and PSCs showed no correlation in amplitude and rise time and occurred at relatively low frequencies of 10-40 Hz during the down state. The number of synaptic inputs during up states, estimated from the up-state charge and the unitary charge of down-state PSCs, was 217 ± 44. Given the average up-state duration of 284 ± 34 msec, synaptic input frequency was ∼800 Hz during up-states for both neuronal types. Many down-state events reversed at the chloride reversal potential and were blocked by GABAA antagonists. The high correlation between up- and down-state reversal potential suggests that despite these drastic changes in synaptic input frequency, the ratio of inhibitory to excitatory currents is similar during both states.